1. Field of the Invention
This invention relates to an instrument and a method for the detection of chemical analytes and physical forces in trace amounts using a coated surface of a microcantilever and measurement after imposing a photo-induced stress on the device.
2. Description of the Prior Art
Microeletromechanical structures are ultra-sensitive fabricated polycrystalline or single crystal devices useful for the measurement of physical forces and chemical interactions.
Vibrating quartz sensors have been used to measure antigen-antibody reactions as described in U.S. Pat. No. 4,236,893 to Rice. The detection of specific chemicals using chemical coatings over quartz crystals to obtain a bulk acoustical wave or surface acoustical wave resonator matrix detector is disclosed by Balato, U.S. Pat. No. 4,596,697. The measurement of ambient gas concentrations with a coated quartz piezoelectric crystal was disclosed by Minten et al., U.S. Pat. No. 4,637,987.
Improved sensors for immunoassays using surface acoustic waves on piezoelectric crystals are disclosed in U.S. Pat. No. 4,735,906 to Bastiaans, U.S. Pat. No. 4,847,193 to Richards et al., U.S. Pat. No. 5,501,986 to Ward et al., U.S. Patent No. 5,595,908 to Fawcett et al., U.S. Pat. No. 5,658,732 to Ebersole et al. and U.S. Pat. No. 5,705,399 to Larue. All of the above acoustical wave detectors are limited to exposure of a single reactive surface.
MEMS devices offer the potential of faster response, alternative methods of measurement of the observed changes, and smaller size.
Binnig et al., Phys. Rev. Lett. 56, 930 (1986) reported the use of a microfabricated beam as a mechanical stylus, which became the basis for atomic force microscopes. Detection with a split-segment photodetector allows measurement of very small movements at the cantilever tip. In 1992, Hoh et al. [J. Am. Chem. Soc., 114, 4917 (1992)] reported the resolution of hydrogen bonds at a force of 1.times.10.sup.-11 N using v-shaped cantilevers of Si.sub.3 N.sub.4.
Vibrating quartz crystal detectors in the shape of a tuning fork are disclosed for the detection of antibodies and other binding pairs in U.S. Pat. No. 5,179,028 to Vali et al. A refinement of the Vali et al. patent may be found in U.S. Pat. No. 5,323,636 which employs the tuning fork concept using GaAs for the substrate.
Gimzewski et al. reported the use of a coated Si cantilever as a micro-calorimeter using reflected light to measure the degree of bending of a cantilever as the result of a chemical reaction. [Chem. Phys. Lett., 217, 589 (1994)]. U.S. Pat. No. 5,411,709 to Furuki et al. discloses a method for gas detection using a vibrating microcantilever coated with a thin film of a dye which fluoresces or phosphoresces in the presence of an oxidizing or reducing gas.
Wachter et al., U.S. Pat. No. 5,445,008 describes a chemical vapor detector using a piezoelectric vibrated cantilever coated with a compound-selective surface having substantially exclusive affinity for the targeted compound. Upon attachment of the targeted compound to the surface coating, the resonance frequency of the vibrating cantilever changes in a concentration-dependant way as measured by the reflected beam from a laser diode received by a photodiode detector.
Properly coated microcantilevers can be used for sophisticated detection taking advantage of both the change in resonance frequency but also stress-induced bending of the sensor, as described and claimed in U.S. Pat. No. 5,719,324 to Thundat et al. A summary of uses for microcantilever sensors may be found in Thundat et al., Microscale Thermophysical Enoineering 1, 185 (1997).
The methods described above are subject to variations in coatings and require many different devices for any spectrum of detection. In addition, accurate quantitation of the result over a range of concentrations becomes more difficult because of the need to be able to measure absolute values of deflection when resonance methods are not used.